Samuel Z. Soffer, MD

Associate Investigator, The Feinstein Institute for Medical Research

Director, Pediatric Surgery Training Program, Cohen Children’s Medical Center

Associate Professor, Surgery and Pediatrics, Hofstra Northwell School of Medicine

Phone: (718) 470-3636
Email: ssoffer@Northwell.edu

About the Investigator

Samuel Soffer, MD joined Cohen Children’s Hospital from the Columbia University College of Physicians and Surgeons and the Children’s Hospital of New York- Presbyterian where he completed his fellowship in pediatric surgery. He received his BA magna cum laude from Yeshiva University (1989) and graduated from SUNY- Downstate Medical School (1996) where he was awarded The Samuel L. Kountz award for Clinical Excellence in surgery. His return to Northwell Health was a homecoming of sorts since he completed his general surgical training at the Long Island Jewish Medical Center in 2003. During his surgical training, Dr. Soffer spent two additional years as a Research/Extracorporeal Life Support fellow at Columbia University.

Dr Soffer has been an active researcher throughout his career with numerous basic science and clinical publications to his credit. His research interests focus on angiogenesis and metastasis in pediatric solid tumor models and the use of anti-angiogenic and anti-metastatic therapies to achieve lasting tumor suppression. Dr Soffer has won awards for his research and has successfully completed several grants that have funded his work. He is the author of more than 35 peer reviewed publications, 5 book chapters, and many national and international presentations. He has mentored multiple surgical residents in his laboratory, several of whom have gone on to become academic pediatric surgeons. Dr Soffer is American Board of Surgery certified in both General and Pediatric Surgery. His clinical practice is confined to Pediatric Surgery and his special interests include complex neonatal surgery, pediatric minimal invasive surgery, and pediatric surgical oncology.

Research Focus

Ewing Sarcoma is the second-most common bone and soft tissue malignancy of childhood. The long-term prognosis for patients with metastatic Ewing Sarcoma is poor, and more than two-thirds of these children will succumb to their disease within five years. Multi-agent chemotherapy is the mainstay of treatment, complemented by surgery and radiation for local control of the primary tumor site or isolated metastatic disease. Although these modalities may be successful for limited, local disease, metastatic Ewing Sarcoma continues to be a great challenge with few effective treatments. New therapeutic options are urgently needed to address these high-risk patients.

Macrophages are phagocytic derivatives of circulating bone marrow-derived monocytes. Upon infiltration into tissues, macrophages serve a variety of homeostatic and immunoregulatory roles important to the adaptive and innate inflammatory responses. Similar to other immunoregulatory cells, macrophages exist in a spectrum of functional states, the extremes of which can be generally characterized by the pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Macrophages that infiltrate and subsequently comprise a substantial portion of the tumor microenvironment are termed tumor-associated macrophages (TAMs). TAM-induced malignant progression is reflected by a number of studies on various human tumor specimens that correlate overexpression of macrophage chemoattractants, as well as increased numbers of infiltrating macrophages, with worse prognoses. There is also increasing evidence that macrophages play an important role in establishing the “premetastatic niche,” altering the stromal environment at sites far from the primary tumor and enhancing extravasation and growth of metastatic cells. Few studies have examined the role of macrophages in Ewing Sarcoma, although some evidence suggests that TAMs may promote Ewing Sarcoma disease progression. CNI-1493, also known as semapimod, is a small molecule anti-inflammatory agent that has been shown to inhibit production of macrophage-derived inflammatory mediators without significantly affecting other cell lineage. Although the mechanism of action remains to be delineated, CNI-1493 has been deemed safe and well tolerated in humans, having completed a phase II clinical trial for Crohn’s disease without significant adverse side effects [41-44]. Given its safety profile, CNI-1493 has recently been identified as a possible TAM-targeting antitumor agent.

In our lab we have discovered that CNI-1493 markedly decreases the incidence of invasive metastasis and tumor burden in a mouse model of Ewing Sarcoma, and that it suppresses M2 macrophage-stimulated tumor cell invasion and extravasation in vitro. We are also studying the relationship between metastases and the cyclooxygenase pathway focusing on the potential for commercially available COX-2 inhibitors, used as anti-inflammatory agents, as potential anti-metastatic agents. Our goal is to develop an up-front anti-metastatic regimen for pediatric solid tumors that have high metastatic potential which when coupled with surgical excision of the primary tumor and standard adjuvant therapies will lead to enhanced long term survival.

Lab Members

Christopher Behr, MD
Research Fellow, Surgical Resident
Research: Studies novel therapeutic drugs that could be used to block tumor invasion.
Email: cbehr@Northwell.edu

Education

State University of New York – Downstate Medical Center, Brooklyn, NY
Degree: MD
1996

Yeshiva University, New York, NY
Degree: BA, magna cum laude
1989

POSTDOCTORAL TRAINING

Pediatric Surgery Chief Resident – 2005
Children’s Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY

Associate Pediatric Surgery Chief Resident – 2004
Children’s Hospital of New York, Columbia University College of Physicians and Surgeons, New York, NY

Chief Surgical Resident – 2003
Northwell Health, New Hyde Park, NY

Senior Surgical Resident – 2002
Northwell Health, New Hyde Park, NY

Research/ECMO Fellow – 2001
Division of Pediatric Surgery, Columbia University College of Physicians and Surgeons, New York, NY

General Surgery Intern/Resident – 1999
Long Island Jewish Medical Center

Honors and Awards

2011 Best Poster Presentation, New York Chapter, American College of Surgeons
2002-2003 Department of Surgery Resident Research Award, Long Island Jewish Medical Center
2001-2002 Department of Surgery Resident Research Award, Long Island Jewish Medical Center
2000-2001 Department of Surgery Resident Academic Award, Highest In-Service Score,
Long Island Jewish Medical Center

Best Poster,Northwell Health Department of Surgery Resident Research Symposium
Murry Friedman Competition, 2nd Place Basic Science Research New York Surgical Society
Academic Day Competition, Best Basic Science Paper, Feinstein Institute for Medical Research
Rosenkrantz Resident Research Award, Poster Presentation, American Academy of Pediatrics,
Section on Surgery
Rosenkrantz Resident Research Award, 8 Minute Presentation/Basic Science,
American Academy of Pediatrics, Section on Surgery
Rosenkrantz Resident Research Award, 3 Minute Presentation/ Clinical,
American Academy of Pediatrics, Section on Surgery
Samuel L. Kountz Award for Clinical Excellence in Surgery, Graduation Honors Ceremony,
SUNY-Downstate Medical Center

Publications
  1. Hesketh A, Behr C, Soffer SZ, Hong A, Glick R. “Neonatal esophageal perforation: non-operative management.” , Journal of Surgical Research. Accepted January 2015.
  2. Behr C, Hesketh A, Barlow M, Glick R, Symons M, Steinberg B, Soffer SZ. “Celecoxib inhibits Ewing Sarcoma Cell Migration via Actin Modulation. Journal of Surgical Research. Accepted January 2015.
  3. Behr CA, Hesketh AJ, Soffer SZ, Edelman M, Glick, RD. Primary retroperitoneal mucinous cystadenoma: an unusual cause of abdominal mass in a child, Journal of Pediatric Surgery Case Reports, 2 (2): 61-63, 2014
  4. Barlow M, Edelman M, Glick RD , Steinberg BM, Soffer SZ. Celecoxib Inhibits Invasion and Metastasis via a COX-2 Independent Mechanism in an in vitro Model of Ewing’s Sarcoma, Journal of Pediatric Surgery, 47(6) : 1223-27, 2012
  5. Gendy AS, Glick RD, Edelman M, Barlow M, Steinberg BM, Soffer SZ. Combination antiangiogenic therapy inhibits anti-vascular endothelial growth factor tachyphylaxis and prolongs survival in a murine model of Ewing’s sarcoma, Journal of Molecular Medicine, Pending revisions
  6. Gendy AS, Glick RD, Hong AR, Dolgin SE, Soffer SZ, Landers H, Herrforth M, Rosen NG: A comparison of the Cleft Lift procedure versus wide excision and packing for the treatment of pilonidal disease in adolescents. Journal of Pediatric Surgery 46(6):1256-1259, 2011
  7. Gendy AS. Lipskar A, Glick RD, Steinberg BM, Edelman M, Soffer SZ. Selective inhibition of   cyclooxygenase-2 (cox-2) suppresses metastatic disease without affecting   primary tumor growth in a murine model of Ewing’s sarcoma. Journal of Pediatric Surgery, 46: 108-114, 2011
  8. Issaivanan M, Redner A, Weinstein T, Soffer SZ, Glassman L, Edelman M , Fein-Levy C. Esophageal Carcinoma in Children and Adolescents, Journal of Pediatric Hematology and Oncology, J Pediatr Hematol Oncol 2012; 34(1): 63- 67.
  9. Manglik N,. Kahn LB, , Edelman M, , Soffer SZ, Mansoor N. Melanotic Neuroectodermal Tumor of Infancy: An Unusual Location. Archives of Pathology & Laboratory Medicine, 134: 1283-1396, 2010
  10. Lipskar A, Soffer SZ, Glick RD, Rosen N, Hong A. Laparoscopic Inguinal Hernia Inversion and Ligation. Journal of Pediatric Surgery, 45: 1370-1374, 2010

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